Research Project 2 Molecular, viral and genetic epidemiology of virally induced AIDS-defining cancers affecting Argentina population with highest risk for HIV infection

研究项目 2 影响艾滋病毒感染风险最高的阿根廷人口的病毒引起的艾滋病定义癌症的分子、病毒和遗传流行病学

• 批准号: 10488070
• 负责人: Pedro Enrique Cahn
• 金额: $ 13.07万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10488070
• 关键词: AIDS related cancer; AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Acyclovir; Address; Affect; Animal Model; Anti-Retroviral Agents; Anus; Area; Argentina; Argentine; Award; Basic Science; Biological; Blood specimen; CD4 Lymphocyte Count; Cancer Burden; Caring; Cell Line; Cells; Characteristics; Chlamydia; Clinical; Clinical Data; Cohort Studies; Collaborations; Collection; Communities; Coupled; Cytology; DNA Virus Infections; Development; Diagnosis; Disease; Drug usage; Enrollment; Epidemiology; Funding; Gene Expression; General Population; Genes; Genetic Determinism; Genetic study; Genomics; Goals; HIV; HIV Infections; HIV Seronegativity; HIV Seropositivity; Health; Health Services Accessibility; Health system; High Prevalence; Hormones; Hospitals; Human; Human Herpesvirus 8; Human Papillomavirus; Human papilloma virus infection; In Vitro; Incidence; Income; Individual; Infection; International; Intervention; Kaposi Sarcoma; Knowledge; Lesion; Life Expectancy; Location; Longitudinal Studies; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of anus; Modeling; Molecular; Molecular Abnormality; Molecular Epidemiology; Molecular Genetics; Monitor; Mutation; North America; Oncogenic; Oral; Pathologic; Patients; Peripheral Blood Mononuclear Cell; Persons; Pharmaceutical Preparations; Policies; Population; Portraits; Positioning Attribute; Prevalence; Prospective cohort; Reduce health disparities; Registries; Research; Research Personnel; Research Priority; Research Project Grants; Research Support; Research Training; Risk Factors; Sampling; Serology; Site; South America; Specimen; Subgroup; Syphilis; Testing; Time; Tissue Sample; Treatment outcome; Tumor Tissue; United States National Institutes of Health; Variant; Viral; Viral Epidemiology; Viral Load result; Viral hepatitis; Viremia; Virus; Virus Diseases; Work; advocacy organizations; base; cancer risk; career; co-infection; cohort; comorbidity; driver mutation; exome sequencing; genetic epidemiology; high risk; high risk population; improved; in vivo; low and middle-income countries; men; neoplastic; premalignant; prospective; repository; research clinical testing; sex; social structure; transcriptome; transcriptome sequencing; transcriptomics; transgender; transgender women; transsexual; transvestite; treatment disparity; treatment response; tumor; working group

RESEARCH PROJECT 2 SUMMARY JULY 2017-JUNE 2023 Men having sex with men (MSM) and transgender women (TGW) are the most affected populations by HIV, present high prevalence of KSHV and HPV, and two malignant conditions associated to these virus (Kaposi Sarcoma and Anal Squamous Cell Carcinoma, respectively) are also disproportionally affecting these groups. KS continues being the most important AIDS associated cancer in LMICs. On the other hand, ART changed the course of HIV and increased life expectancy, but HPV persistence represents a continued risk factor for anal cancer. The aims of this project are 1) to increase the knowledge about prevalence, incidence, and clearance of KSHV and HR-HPV among high risk individuals (MSM and TG individuals with and without HIV) and factors associated to clinical progression 2) to create a repository of prospective and retrospective samples of KS and ASCC cou- pled to clinical data and 3) to explore in KS and ASCC the molecular portrait and viral factors by Whole-Exome sequencing in parallel with RNA-Seq profiling comparing the mutational and gene expression profiles of samples for identify specific transcriptome. We will accomplish these aims studying two populations: a) a cohort of individuals at high risk of developing KS and ASCC 220 MSM and 110 transgender women, HIV positive and HIV negative) in whom we will assess every 6 months during 4 years the prevalence, incidence, and associated factors for KSHV infection and HPV infection. c) a repository of clinical information and biological samples of individual with KS and ASCC. This registry will involve two components, the prospective component that will collect clinical data and samples from patients in study for KS or ASCC (15-30/year) and a retrospective component aimed to provide limited clinical information and remnants of pathological specimens at 6 sites (400 KS and 200 ASCC). All the material will be available also for Basic and Translational Projects 1 and 2. With these aims our research contributes to several areas defined by NIH as high priority research on HIV/AIDS, including the focus in malignances, basic research on genetic determinants of co-morbidities and research to reduce health disparities in the treatment outcomes of people living with HIV. Further, this research will support research capacity development in a low- and middle-income settings. Accordingly, we aim to address several urgent health questions, which will inform the development of a range of policies and interventions throughout South and North America. The long-term objective of this study is to catalyze international collaboration among US and Argentinean investigators to improve capacity to reduce the cancer burden among HIV individuals.

研究项目2摘要 2017年7月至6月2023年 男性与男性发生性关系（MSM）和跨性别女性（TGW）是艾滋病毒受影响最大的人群 当前KSHV和HPV的患病率很高，以及与这些病毒相关的两个恶性疾病（Kaposi 肉瘤和肛门鳞状细胞癌） 也对这些群体的影响也不成比例。 KS继续是LMIC中最重要的艾滋病癌症。另一方面，艺术改变了 艾滋病毒的过程和增加的预期寿命，但HPV持久性代表了肛门的持续风险因素 癌症。 该项目的目的是1）增加有关KSHV患病率，发病率和清除的知识 高风险个体（有和没有艾滋病毒的MSM和TG个体）和相关因素中的HR-HPV 到临床进展2）创建KS和ASCC cou-的前瞻性和回顾性样本的存储库 代表临床数据，3）在KS和ASCC中探索全外象征的分子肖像和病毒因子 与RNA-seq分析并行测序，比较样品的突变和基因表达谱 识别特定的转录组。 我们将完成研究两个人群的这些目标：a）一个具有高风险发展KS的个体 和ASCC 220 MSM和110名变性妇女，艾滋病毒阳性和艾滋病毒负面），我们将评估每一个 在4年内6个月的患病率，发病率以及KSHV感染和HPV感染的相关因素。 c）KS和ASCC个体的临床信息和生物样本的存储库。该注册表将 涉及两个组件，即将收集临床数据和患者样本的前瞻性组成部分 KS或ASCC的研究（15-30/年）和回顾性组件旨在提供有限的临床信息 和在6个地点（400 KS和200 ASCC）处的病理标本的残留物。所有材料都将可用 也适用于基本和翻译项目1和2。 通过这些目标，我们的研究为NIH定义为艾滋病毒/艾滋病的高优先研究所定义的几个领域， 包括在恶性肿瘤上的重点，对合并症的遗传决定因素的基础研究和研究 减少艾滋病毒患者的治疗结果中的健康差异。此外，这项研究将支持 低收入和中等收入环境中的研究能力发展。因此，我们旨在解决一些 紧急健康问题，这将为整个政策和干预措施的制定提供信息 南美和北美。这项研究的长期目标是促进国际合作 美国和阿根廷的研究人员可以提高减轻艾滋病毒个体癌症负担的能力。